The widespread use of radiation in such areas as medicine, agriculture and industry, along with the elevating threat of nuclear terrorism, has made radiation-induced normal tissue damage an increasing focus of concern for both civilians and the military. Thus, the need to identify radioprotectors that effectively reduce the biological effects of radiation, but lack the unwanted side effects associated with current radioprotectors, has taken on increasing urgency. In this regard, we have recently reported a dose-dependent relationship between Asian ginseng extracts and radioprotection in human peripheral blood lymphocytes (PBL) ex vivo. We believe this ex vivo radioprotection is indicative of ginseng's potential to function as an effective radioprotector in vivo. Our specific hypothesis is that ginseng possesses the potential to be an effective radioprotector in vivo, and, since free radicals play such an important role in radiation-induced damage, the mechanism underlying this radioprotection is linked, either directly or indirectly, to its antioxidative ability. Using a standardized North American Ginseng extract (NAGE) as our radioprotective agent, the specific aims are to: 1. Define the radioprotective potential of NAGE using our ex vivo PBL model by determining the effect of NAGE on PBL, before and after exposure to radiation, based on the degree of DNA damage; 2. Identify whether the mechanism underlying NAGE's radioprotection is correlated with its antioxidative action by assessing the cellular oxidative/antioxidative status in PBL before and after the radiation exposure and/or NAGE administration; and 3. Determine whether oral, daily supplementation of NAGE to healthy human subjects results in radioprotection of their PBL by comparing, both before and after administration of NAGE, the radiation-induced DNA damage in PBL drawn from subjects and exposed ex vivo to a range of radiation doses (0-2 Gy). Accomplishing these aims will provide an essential prerequisite to the development of NAGE as an effective radioprotector.